Allele-specific miRNA-binding analysis identifies candidate target genes for breast cancer risk.

NPJ Genomic Medicine
Ana C. Jacinta-FernandesAna-Teresa Maia

Abstract

Most breast cancer (BC) risk-associated single-nucleotide polymorphisms (raSNPs) identified in genome-wide association studies (GWAS) are believed to cis-regulate the expression of genes. We hypothesise that cis-regulatory variants contributing to disease risk may be affecting microRNA (miRNA) genes and/or miRNA binding. To test this, we adapted two miRNA-binding prediction algorithms-TargetScan and miRanda-to perform allele-specific queries, and integrated differential allelic expression (DAE) and expression quantitative trait loci (eQTL) data, to query 150 genome-wide significant ( P ≤ 5 × 10 - 8 ) raSNPs, plus proxies. We found that no raSNP mapped to a miRNA gene, suggesting that altered miRNA targeting is an unlikely mechanism involved in BC risk. Also, 11.5% (6 out of 52) raSNPs located in 3'-untranslated regions of putative miRNA target genes were predicted to alter miRNA::mRNA (messenger RNA) pair binding stability in five candidate target genes. Of these, we propose RNF115, at locus 1q21.1, as a strong novel target gene associated with BC risk, and reinforce the role of miRNA-mediated cis-regulation at locus 19p13.11. We believe that integrating allele-specific querying in miRNA-binding prediction, and data supporti...Continue Reading

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Datasets Mentioned

BETA
SRX513286
GSE35023

Methods Mentioned

BETA
genotyping

Software Mentioned

Ensembl
R
SNP Annotation and Proxy Search 50
miRanda
biomaRt R
SNAP
R package biomaRt
TargetScan
biomaRt R package

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